#KEYNOTE 158 CLINICAL TRIALS.GOV VERIFICATION#

Median overall survival (OS) was 11.7 months (95% CI, 8.2-19.1) in the TMB-H group compared with 13.0 months (95% CI, 11.5-14.6) in the non–TMB-H population. At 2 years, the PFS rates were 18.9% and 6.5% in the TMB-H and non–TMB-H groups, respectively. The rate of PFS at 1 year was 26.4% in the TMB-H group and 14.1% in the non–TMB-H group. The median progression-free survival (PFS) in both the TMB-H and non–TMB-H groups was 2.1 months. The ORR when excluding patients with MSI-H tumors was 27.1% and was 6.7% in the patients with non–TMB-H tumors. The median duration of response (DOR) has not yet been reached, but 57% of patients had responses lasting at least 1 year and 50% having responses lasting at least 2 years.Īccording to prior data presented at the 2019 ESMO Annual Congress, among the patients with TMB-H tumors, the objective response rate (ORR) was 30.3% (95% CI, 21.5%-40.4%) the complete response rate was 4.0% and the partial response rate was 26.3%.

The overall response rate was 29% (95% CI, 21%-39%) with complete responses in 4% of patients and partial responses in 25%. The most common tumor types were mesothelioma (12.7%), neuroendocrine (12.3%), salivary (12.0%), and endometrial (10.3%) in the non–TMB-H group. All patients received 200 mg of intravenous pembrolizumab every 3 weeks until unacceptable toxicity or disease progression.Īmong the patients with TMB-H tumors (n=102), the most common tumor types were small cell lung cancer (34.3%), cervical (16.2%, endometrial (15.2%), and anal (14.1%). Tissue TMB was assessed using the FoundationOne CDx assay and TMB-H status was defined as at least 10 mutations/megabase.

These patients were compared with 652 patients who did not have high TMB. The approval is based off of findings from an analysis of 10 cohorts of patients with various previously treated unresectable or metastatic solid tumors and high TMB from the ongoing phase 2 KEYNOTE-158 trial, which is exploring the use of the PD-1 inhibitor in patients with advanced solid tumors. The FDA also approved the FoundationOneCDx assay as a companion diagnostic for pembrolizumab to identify patients who TMB high solid tumors who may benefit from the immunotherapy.

#KEYNOTE 158 CLINICAL TRIALS.GOV VERIFICATION#

This new indication for pembrolizumab was granted under accelerated approval and may be contingent upon verification of clinical benefit in confirmatory trials. Fakih, MD, professor, Department of Medical Oncology & Therapeutics Research medical director, Judy & Bernard Briskin Center for Clinical Research co-director, Gastrointestinal (GI) Cancer Program and section head, GI Medical Oncology, City of Hope, told Targeted Oncology. When limiting the analysis to the TMB high, non–MSI-H patients, the response rate was still 4-fold that of the non-MSI-H group (24% vs 6%),” investigator Marwan G. A response rate of 29% (versus 6% in patients with a TMB <10) in this biomarker-defined population is quite impressive, especially given the refractory nature of their disease. “KEYNOTE-158 has confirmed clinical activity of pembrolizumab in tumors harboring a TMB ≥10 (TMB-High) across a variety of previously treated solid tumors including anal, biliary, cervical, endometrial, mesothelioma, neuroendocrine, salivary, small cell lung, thyroid, and vulvar cancers. This marks the second tumor-agnostic approval for pembrolizumab, which is also approved for the treatment of patients with microsatellite instability–high (MSI-H) or mismatch repair deficient solid tumors. The FDA has approved pembrolizumab (Keytruda) for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors with tissue tumor mutational burden–high (TMB-H ≥10 mutations/megabase), as determined by an FDA-approved test, who have progressed following prior treatment and have no satisfactory alternative treatment options.

Keynote 158 clinical trials.gov